Methods for delivering a drug to a patient while restricting access to the drug by patients for whom the drug may be contraindicated

ABSTRACT

Methods for delivering a drug to a patients in need of the drug, while restricting access to the drug by patients for whom the drug may be contraindicated are disclosed. The methods are of the type in which prescriptions for the drug are filled by a pharmacy only after a computer readable storage medium has been consulted to retrieve a prescription approval code. Embodiments are provided wherein the patients are assigned to risk groups based upon the risk that taking the drug will lead to an adverse side effect, and certain additional information, such as periodic surveys and diagnostic tests probative of the ongoing risk of the side effect developing are obtained before prescriptions for the drug are approved.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.11/028,144, filed Jan. 3, 2005, now U.S. Pat. No. 7,141,018, which is acontinuation of U.S. application Ser. No. 10/762,880, filed Jan. 22,2004, now U.S. Pat. No. 6,869,399, which is a continuation of U.S.application Ser. No. 10/383,275, filed Mar. 7, 2003, now U.S. Pat. No.6,755,784, which is a continuation of U.S. application Ser. No.09/965,155, filed Sep. 27, 2001, now U.S. Pat. No. 6,561,977, which is acontinuation of U.S. application Ser. No. 09/694,217, filed Oct. 23,2000, now U.S. Pat. No. 6,315,720, the entirety of each of which ishereby incorporated by reference.

FIELD OF THE INVENTION

The present invention relates to improved methods for delivering a drugto a patient. More particularly, the present invention relates to novelmethods for delivering a teratogenic or other potentially hazardous drugto a patient in need of the drug, while avoiding the occurrence of knownor suspected side effects of the drug. The novel methods permit thedistribution to patients of drugs, particularly teratogenic drugs, inways wherein such distribution can be carefully monitored andcontrolled.

BACKGROUND OF THE INVENTION

Many beneficial drugs are known or suspected of producing adverse sideeffects in certain individuals. These side effects may be manifest inthe patient taking the drug, in a foetus (i.e. fetus) carried by thepatient, or in a recipient (or foetus carried by a recipient) of thebodily fluids of the patient. In some cases, administration of the drugmay be acceptable in some patients, but absolutely contraindicated inother patients. For example, drugs known or suspected of causing birthdefects if taken by a pregnant woman (i.e. teratogenic drugs), maynonetheless be beneficial for treating certain conditions. However,because of the teratogenic properties of the drug, administration topregnant women must be avoided. Other drugs are known which may bebeneficially employed in the general population, but must be avoided byindividuals having a certain preexisting condition, or thoseconcurrently taking certain other medication(s), due to adverse sideeffects which may develop in those individuals.

One such drug which is known to produce adverse side effects, but whichmay nevertheless be beneficially employed in certain patients isthalidomide. Thalidomide is a drug which was first synthesized inGermany in 1957. Beginning in 1958, it was marketed in many countriesfor use as a sedative, although it was never approved for use in theUnited States. After reports of serious birth defects, thalidomide waswithdrawn from all markets by 1962. However, during the years it wasused, it was found to be effective in treating erythema nodosum leprosum(ENL), a condition of leprosy, and the U.S. Food and Drug Administration(FDA) has made the drug available for this specific use via a program ofthe Public Health Service. More recently, investigators have found thatthalidomide may be effective in treating AIDS wasting and aphthousulcers occurring in AIDS patients. In addition, treatments for otherdiseases, such as a number of neoplastic diseases including cancers,rheumatoid arthritis, and macular degeneration, are also believed to bepossible. The FDA has recently approved an application by CelgeneCorporation, which is the assignee of the present patent application, tomarket thalidomide for the treatment of ENL. The medical communityanticipates that thalidomide will be used for treatment of additionalconditions and diseases, including those set forth above. However, dueto the severe teratogenic risk of thalidomide, methods are needed tocontrol the distribution of this drug so as to preclude administrationto foetuses.

In this regard, U.S. Pat. No. 6,045,501, to Elsayed et al., providesmethods for delivering a drug to a patient while preventing the exposureof a foetus or other contraindicated individual to the drug. Accordingto the methods of this patent, prescriptions for the drug are filledonly after a computer readable storage medium has been consulted toassure that the prescriber is registered in the medium and qualified toprescribe the drug, that the pharmacy is registered in the medium andqualified to fill the prescription for the drug, and the patient isregistered in the medium and approved to receive the drug. Improvementsto this method may be useful, however, to minimize and simplify thedemands on the pharmacy, thereby improving compliance with the system ofdistribution, and reducing the risk that the drug will be dispensed to acontraindicated individual.

Methods for monitoring and educating patients to whom a drug isdistributed have been developed in connection with Accutane(isotretinoin). Accutane, which is a known teratogen, is a uniquelyeffective drug for the treatment of severe, recalcitrant, nodular acne.A pregnancy prevention program was developed, and the Slone EpidemiologyUnit of Boston University designed and implemented a survey to evaluatethese efforts. The survey identified relatively low rates of pregnancyduring Accutane treatment, which suggests that such a program can beeffective. With more than about 325,000 women enrolled to date in theAccutane survey, it is also clear that such a large-scale study can beconducted. Enrollment in the Accutane survey is voluntary, however.Accordingly, assessing the representativeness of the women who have beenenrolled in the survey has been problematic, and it has been difficultto determine whether the survey results can be generalized to all femaleAccutane users. Thus, an improved survey is needed which would berepresentative of all users of a particular drug, such as thalidomide,who obtain the drug through legal distribution channels. There are alsono mechanisms provided to assure compliance with the program or to limitdistribution of the drug to participants in the survey.

Because drug sharing may frequently occur among AIDS patients, which mayresult in placing a foetus at risk, a program is needed which can beused to educate men and women about the risk of teratogenic drugs, suchas thalidomide. In addition, a system is needed for the controlleddistribution of a drug, in which of all users of the drug, includingprescribers, pharmacies, and patients, may be accountable for theircompliance with methods that may be established to minimize the riskthat a contraindicated individual will be exposed to the drug. Thepresent invention is directed to these, as well as other important ends.

SUMMARY OF THE INVENTION

The present invention is directed to improved methods for delivering adrug to a patient in need of the drug, while avoiding the occurrence ofan adverse side effect known or suspected of being caused by the drug,of the type in which prescriptions for the drug are filled only after acomputer readable storage medium has been consulted to assure that theprescriber is registered in the medium and qualified to prescribe thedrug, that the pharmacy is registered in the medium and qualified tofill the prescription for the drug, and the patient is registered in themedium and approved to receive the drug. In one embodiment of theinvention, there are provided improved methods comprising the steps of:

-   -   a. defining a plurality of patient risk groups based upon a        predefined set of risk parameters for the drug;    -   b. defining a set of information to be obtained from the        patient, which information is probative of the risk that such        adverse side effect is likely to occur if the drug is taken by        the patient;    -   c. in response to the information set, assigning the patient to        at least one of the risk groups; and    -   d. entering the risk group assignment in the medium before the        patient is approved to receive the drug.

The improved methods described herein provide advantageous and effectivemeans for monitoring, controlling and authorizing the distribution topatients of drugs known or suspected of causing adverse side effects.The methods of the present invention include a variety of checks andbalances which serve to limit unauthorized and possibly inappropriatedistribution of the drug. These methods are particularly applicable todistribution of teratogenic drugs, in which case the checks and balancesmay be particularly advantageous for preventing distribution of the drugto patients whose use of the drug may pose an unacceptable risk that afoetus carried by the patient or a recipient of the bodily fluids of thepatient will be exposed to such drugs. Accordingly, the present methodsmay be advantageously used to avoid exposure of foetuses to teratogenicdrugs, thereby avoiding the terrible birth defects which may result fromsuch exposure.

The invention is not limited to the distribution of teratogenic drugs;other potentially hazardous drugs may also be distributed in accordancewith embodiments of this invention and such drugs may be distributed insuch a fashion that persons for whom such drugs are contraindicated willnot receive them. These and other aspects of the invention will becomemore apparent from the present description and claims.

DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS

The present invention is directed generally to methods for the deliveryof drugs known or suspected of causing an adverse side effect,especially teratogenic drugs, to patients. The term “drug,” as usedherein, refers to any substance which is intended for use in thediagnosis, cure, mitigation, treatment or prevention of disease, or toaffect the structure or function of the body. The term “side effect”refers to any abnormality, defect, mutation, lesion, degeneration orinjury which may be caused by taking the drug. The side effect may beone which is likely to arise in the patient or in a foetus (i.e., fetus)carried by the patient. The side effect may also be one which is likelyto arise in a recipient of the bodily fluid of the patient, or foetuscarried by such recipient. The term “likely to arise” means that theside effect known or suspected of being caused by the drug may beexpected to occur at a higher incidence rate in a particular individualor group of individuals.

Generally speaking, the methods of the present invention may bedesirably and advantageously used to educate and reinforce the actionsand behaviors of patients who are taking a drug, as well as prescriberswho prescribe the drug and pharmacies which dispense the drug. As usedherein, the term “prescriber” refers to any individual who is capable ofprescribing drugs, including, for example, a medical doctor. Sucheducation and reinforcement of actions and behavior are often necessaryto ensure proper prescribing and dispensing of the drug, as well aspatient compliance with taking the drug. A wide variety of educationalmaterials may be employed to ensure proper prescribing, dispensing andpatient compliance according to the methods described herein, including,for example, a variety of literature and other materials, such as, forexample, product information, educational brochures, continuingeducation monographs, videotapes and the like which may describe therisks and benefits associated with taking the particular drug andmeasures which may be taken to avoid those risks.

The methods described herein may be advantageously employed to avoiddelivery of one or more drugs known or suspected of causing an adverseside effect to a patient for whom the drugs may be contraindicated. Asused herein, the term “contraindicated” refers to any condition in apatient which renders a particular line of treatment, including theadministration of one or more drugs, undesirable or improper. Thiscondition may be preexisting, or may develop while the patient is takingthe drugs, including conditions which may result directly or indirectlyfrom treatment with the drugs. Thus, contraindicated drugs include, forexample, teratogenic drugs whose administration, for example, topregnant patients is importantly avoided due to the risks to the foetus.Drugs may also be considered “contraindicated,” as the term is usedherein, if use of a drug by patients who are also taking another drug isknown or suspected of producing an adverse side effect in thosepatients, or in a foetus carried by such patients.

The methods of the present invention are especially advantageouslyemployed for the delivery to a patient of a teratogenic drug. Thedelivery of a teratogenic drug to a patient may be advantageouslyachieved with the present methods while substantially (includingcompletely) avoiding the delivery of the drug to a foetus. The term“substantially,” as used in reference to avoiding the delivery of ateratogenic drug to a foetus, generally means that there is an avoidancerate of delivering the drug to a foetus of greater than about 50%.Preferably, the avoidance rate is greater than about 55%, with anavoidance rate of greater than about 60% being more preferred. Even morepreferably, the avoidance rate is greater than about 65%, with anavoidance rate of greater than about 70% being still more preferred. Yetmore preferably, the avoidance rate is greater than about 75%, with anavoidance rate of greater than about 80% being still more preferred. Ineven more preferred embodiments, the avoidance rate is greater thanabout 85%, with an avoidance rate of greater than about 90% being yetmore preferred. Still more preferably, the avoidance rate is greaterthan about 95%. In particularly preferred embodiments, a teratogenicdrug may be delivered to patients with completely no delivery tofoetuses (i.e., 100% avoidance rate).

The drug delivery methods of the present invention preferably involve,inter alia, registering in a computer readable storage mediumprescribers who are qualified to prescribe the involved drug, including,for example, teratogenic drugs. Once registered in the computer readablestorage medium, the prescriber may be eligible to prescribe the drug topatients in need of the drug. Generally speaking, in order to becomeregistered in the computer readable storage medium, the prescriber maybe required to comply with various aspects of the methods describedherein including, for example, providing patient education andcounseling, and the like, as described in detail below. The registrationof the prescriber in the computer readable storage medium may beachieved by providing the prescriber, for example, by mail, facsimiletransmission, or on-line transmission, with a registration card or form,preferably together with appropriate educational materials concerning,for example, the particular drug for which the prescriber is beingregistered to prescribe, as well as suitable methods for delivering thedrug to the patient, including the drug delivery methods describedherein. The prescriber will preferably complete the registration card orform by providing information requested therein, and the registrationcard or form will preferably be returned to the manufacturer ordistributor of the drug, or other authorized recipient of theregistration materials, for example, by mail, facsimile transmission oron-line transmission. Information which may be requested of theprescriber in the registration card or form may include, for example,the prescriber's name, address, and affiliation, if any, with one ormore health care institutions. The prescriber's information in theregistration card or form is then entered into the computer readablestorage medium. It is contemplated that the registration of theprescriber into the computer readable storage medium may also beachieved, for example, by telephone, and/or through the use of anintegrated voice response system. Suitable computer readable storagemedia which may be employed for registration of the prescribers (as wellas the pharmacies and patients, as discussed below) will be apparent toone of ordinary skill in the art, once armed with the teachings of thepresent application.

In accordance with the methods described herein, pharmacies who arequalified to fill prescriptions for the particular drug being prescribedincluding, for example, teratogenic drugs, are also preferablyregistered in a computer readable storage medium. The computer readablestorage medium in which the pharmacies are registered may be the sameas, or different from the computer readable storage medium in which theprescribers are registered. Once registered in the computer readablestorage medium, the pharmacies may be eligible to dispense the involveddrug to patients who are in need of the drug. Generally speaking, inorder to become registered in the computer readable storage medium, thepharmacy may be required to comply with various aspects of the methodsdescribed herein including, for example, registering the patient(preferably also in a computer readable storage medium), ensuring thatthe patient complies with certain aspects of the drug delivery methods,as well as other aspects of the present methods, as described in detailbelow. As with the registration of the prescriber in the computerreadable storage medium, the registration of the pharmacy may beachieved by providing the pharmacy, for example, by mail, facsimiletransmission, or on-line transmission, with a registration card or form,preferably together with appropriate educational materials concerning,for example, the particular drug for which the pharmacy is beingregistered to dispense, as well as suitable methods for delivering thedrug to the patient, including the drug delivery methods describedherein. The pharmacy may then have the registration card or formcompleted by providing the information requested therein, whichthereafter may be returned to the manufacturer or distributor of thedrug, or other authorized recipient of the registration card or form,for example, by mail, facsimile transmission or on-line transmission.Information which may be requested of the pharmacy in the registrationcard or form may include, for example, the pharmacy's name, address, andaffiliation, if any, with any health care institution such as, forexample, a hospital, health care organization, and the like. Thepharmacy's information in the registration card or form is thenpreferably entered into the computer readable storage medium. It iscontemplated that the registration of the pharmacy into the computerreadable storage medium may also be achieved, for example, by telephoneand/or through the use of an integrated voice response system.

As noted above, the drug delivery methods described herein alsopreferably involve the registration of the patient in a computerreadable storage medium. The computer readable storage medium in whichthe patients are registered may be the same as, or different from thecomputer readable storage medium in which the prescriber and/or pharmacyis registered. Generally speaking, in order to become registered in thecomputer readable storage medium, the patient may be required to complywith various aspects of the methods described herein. The registrationof the patient may be carried out by the registered pharmacy, forexample at the time of the patient's initial visit to the pharmacy. Ithas been found, however, that it may be more efficient, and bettercompliance with the methods of the present invention may be provided, ifregistration of the patient is carried out by the registered prescriberof the drug at the time the initial prescription is generated.

In preferred form, the prescriber will typically have a registrationcard or form filled out for the patient, which includes information onthe patient, such as the patient's name, sex, mailing address, date ofbirth, and the like. Information on the prescribing prescriber anddispensing pharmacy, such as the information described above for theregistration thereof, may also be desirably entered on the patientregistration card or form. The completed card or form may then beforwarded to the manufacturer or distributor of the drug, or otherauthorized recipient of the registration form, for example, by mail,facsimile transmission or on-line transmission. Where registration is bymail or facsimile, entry of the registration into the computer readablestorage medium may preferably include the use of optical characterrecognition (OCR) software. It is also possible that the registration ofthe patient into the computer readable storage medium may also beachieved, for example, by telephone and/or through the use of anintegrated voice response system.

Preferably, information will also be collected from the patient that maybe probative of the risk that a known or suspected side effect willoccur if the drug is taken by the patient. This information may then becompared with a predefined set of risk parameters for the drug, which inturn define a plurality of risk groups, so that analysis of theinformation will permit assignment of the patient to at least one of therisk groups. Preferably, this risk group assignment is then also enteredinto the computer readable storage medium. This assignment may beperformed by the prescriber, who may then include the risk groupassignment on the patient's registration card or form, or may beperformed by another individual, such as a nurse, technician, or officepersonnel, who preferably interprets the information and assigns thepatient to one of the risk groups, accordingly.

As discussed above, it is preferable that a plurality of risk groups,each based upon a predefined set of risk parameters, be established forthe drug which is to be administered. As will be evident to those ofskill in the art, the risk parameters to be considered and the riskgroups defined by those parameters, will be based upon factors whichinfluence the risk that a known or suspected adverse side effect willoccur if the patient receives the drug, and will vary depending upon thedrug in question. Where the drug is a teratogenic drug, for example,such risk parameters may include elements which would impact the risk ofa foetus being exposed to the drug, such as the age, sex andreproductive status of the patient. For example, a first risk group maycomprise female patients of child bearing potential; a second risk groupmay comprise female patients of non-child bearing potential; a thirdrisk group may comprise sexually active male patients; and a fourth riskgroup may comprise sexually inactive male patients. Additionally, theremay be a risk group established for patients to whom administration ofthe drug may be strictly contraindicated, and patients assigned to sucha group will not be approved to receive the drug. For other drugs,different factors, such as those influencing the likelihood that certainpreexisting conditions may exist, or the likelihood of certain otherdrugs being used concomitantly with the prescribed drug, may define therelevant risk parameters.

By assigning each patient to a risk group, the steps that will be takento minimize the chance that the drug is dispensed to a contraindicatedpatient, and to minimize the risk that a known or suspected adverse sideeffect will occur, can be tailored to suit the circumstances of thatparticular patient. For example, depending upon which risk group apatient is assigned to, additional information may be collected from thepatient. As discussed more fully below, such additional information maybe in the form, for example, of a patient survey. Such additionalinformation may also include the results of certain diagnostic testswhich have been performed. Based upon the additional information, thepatient's risk group assignment may then remain the same, or the patientmay be assigned to a different risk group, which may in turn requirethat further additional information be collected from the patient.

In accordance with the present invention, the monitoring of two, threeor more drugs either administered to or proposed for administration to apatient may also be accomplished in order to avoid or diminish thelikelihood of the occurrence of one or more side effects. Thus,combinations of drugs which, when administered to an individual patient,may give rise to an increased likelihood of side effects, may beregistered in a computer readable storage medium, and the patient's riskgroup assignment may be reflective of this increased risk. A physicianis registered to prescribe at least one of the drugs for a patient and apharmacy is registered to fill such prescription. In this way, throughassignment of such patient to one or more risk groups, the avoidance ofharmful drug interactions may be attained.

It is preferred that for any given risk group, there may be defined apredetermined additional set of information which is to be collectedfrom the patient. This additional set of information may be obtainedprior to the initial dispensation of the drug to the patient and/or maybe obtained from the patient on a periodic basis. This information mayinclude information not previously obtained from the patient, or maysimply reiterate previously asked questions, and repeat diagnostic testswhich were conducted previously. The information may relate to thepatient's conduct, or may relate to the patient's past or ongoingmedical treatment, such as other procedures or medication which thepatient may have received or is still receiving. For example, theadditional set of information may be in the form of a survey orquestionnaire regarding the patient's behavior and compliance with riskavoidance measures and may thus be probative of whether the risk ofoccurrence of an adverse side effect has increased, decreased orremained the same. Based upon the responses by the patient, thepatient's risk group assignment may, if appropriate, be changedaccordingly. Alternatively, where side effects which are known orsuspected of being caused by a combination of drugs, the questions askedof the patient may be probative of the likelihood that the patient maytake such a combination of drugs. Similarly, where sharing of drugs bythe patient may be a matter of concern, the survey may be probative ofthe risk that the patient may be sharing the hazardous drug withanother, and hence increase the risk that a contraindicated individualmay receive the drug.

The additional information may also include the results of certaindiagnostic tests which have been performed on the patient. Suchdiagnostic tests may be probative, for example, of the risk of exposureof a foetus to a teratogenic drug, may test for the presence of a riskfactor for the adverse side effect of concern, or may be probative ofthe onset of that side effect. Where the use of combinations of morethan one drug are known or suspected of causing an increased risk of theoccurrence of a side effect, the diagnostic testing may include testingfor the presence of one or more of those drugs, or evidence of the useby the patient of such other drugs. Additionally, diagnostic tests maybe probative of the concentration of one or more drugs, including theprescribed drug or drugs, to assure that appropriate dosing ismaintained.

Such diagnostic testing may be conducted on any bodily fluid or wasteproduct of the patient, including the blood, serum, plasma, saliva,semen or urine, as well as the feces. Diagnostic testing may also beperformed on a biopsy of any tissue of the patient or may includegenetic testing, which may be indicative of a genetic predisposition toa particular adverse side effect. Other forms of diagnostic testing,such as diagnostic imaging, or tests which may be probative of theproper functioning of any tissue, organ or system are also contemplated.Preferably, the additional information and/or diagnostic test resultsare obtained and entered in the computer readable storage medium beforethe patient is approved to receive the drug. Additionally, where theinformation indicates that the risk of the adverse side effect occurringoutweighs the potential benefit of the drug, the patient may be assignedto a risk group that will preclude approval of dispensation of the drugto that patient.

In accordance with the methods of the present invention, therefore, thedelivery of the drug to the patient may involve the following steps. Asa prelude to prescribing and dispensing the drug to the patient, theprescriber and the pharmacy are registered in one or more appropriatecomputer readable storage media, as described above. If the prescriberis not registered in the computer readable storage medium, theprescriber will be ineligible to prescribe the drug. Similarly, if thepharmacy is not registered in the computer readable storage medium, thepharmacy will be ineligible to dispense the drug.

In the course of an examination of a patient, including patientssuffering from one or more diseases and/or disorders such as, forexample, erythema nodosum leprosum (ENL), the prescriber may determinethat the patient's condition would be improved by the administration ofa drug such as, for example, a teratogenic drug, including thalidomide.Prior to prescribing the drug, the prescriber preferably counsels thepatient, for example, on the various risks and benefits associated withthe drug. For example, the prescriber preferably discusses the benefitsassociated with taking the drug, while also advising the patient on thevarious side effects associated therewith. In embodiments of theinvention wherein the prescriber assigns the patient to a specific riskgroup, the disclosure is preferably tailored to that risk groupassignment. Thus, a patient who may acquire or impart a condition ordisease for which the drug is contraindicated is preferably counseled bythe prescriber on the dangers associated therewith and advised as torisk avoidance measures which may be instituted. Preferably the patientis provided full disclosure of all the known and suspected risksassociated with taking the drug. For example, in the case of teratogenicdrugs, the prescriber preferably counsels the patient on the dangers ofexposing a foetus, either one which may be carried by the patient or onecarried by a recipient of the bodily fluids of the patient, to theteratogenic drug. Such counsel may be provided verbally, as well as inwritten form. In preferred embodiments, the prescriber provides thepatient with literature materials on the drug for which a prescriptionis contemplated, such as product information, educational brochures,continuing education monographs, and the like. Thus, in the case ofmethods involving teratogenic drugs, the prescriber preferably providespatients with literature information, for example, in the form of theaforesaid product information, educational brochures, continuingeducation monographs, and the like, warning the patient of the effectsof the drug on foetuses. In the case of other drugs which are known orsuspected of causing an adverse side effect, the patient is counseled asto the dangers of taking the drugs, and of steps which may be taken toavoid those risks. For example, if the concomitant use of the drug andanother drug, for example alcohol, is to be avoided, the prescriberadvises the patient of the risks of drinking alcohol while taking thedrug.

With particular reference to counseling provided in connection withteratogenic drugs, the prescriber preferably counsels female patientsthat such drugs must never be used by pregnant women. If the patient isa female of child-bearing potential (i.e., a woman who is capable ofbecoming pregnant), the prescriber preferably counsels the patient thateven a single dosage of certain teratogenic drugs, such as thalidomide,may cause birth defects. Accordingly, the patient is preferablycounseled to avoid sexual intercourse entirely, or if sexually active,to use appropriate forms of contraception or birth control. For bothmale and female patients, the prescriber preferably provides counsel onthe importance of using at least two forms of effective birth controlmethods, with one form preferably being a highly effective hormonalmethod, and the other form preferably being an effective barrier method.The patients are preferably counseled to use the birth control methodsfor a period of time prior to and during treatment with the teratogenicdrug, as well as for a period of time after treatment with the drug hasbeen terminated. In preferred embodiments, the patient is counseled touse at least two forms of birth control for at least about 4 weeks priorto initiation of treatment, during treatment, and for at least about 4weeks after treatment has been terminated. It may be desirable for theprescriber to personally provide female patients who are capable ofbecoming pregnant with one or more contraceptive devices orformulations.

Male patients who are being prescribed a teratogenic drug are preferablycounseled to use condoms every time they engage in sexual relations,since many teratogenic drugs may be found in semen. Male patients arealso preferably counseled to contact their prescriber if they havesexual intercourse without a condom, and/or if it is believed that theymay have caused a pregnancy. As with female patients, it may bedesirable for the prescriber to provide male patients who are capable ofimpregnating female patients with a contraceptive device or formulation.Other advice relative to birth control that the prescriber may provideto the patient would be apparent to one skilled in the art, once armedwith the teachings of the present application. If the prescriber who isprescribing the teratogenic drug is unaware of certain aspects of theavailable forms of birth control and the advantages and disadvantagesassociated therewith, the patient should be referred to a prescriber whois knowledgeable on such matters, prior to be being prescribed theinvolved drug. Generally speaking, as discussed below, counseling onteratogenecity, birth control, and the like is preferably given only tofemale patients who are capable of becoming pregnant, or to malepatients who are capable of having sexual relations with partners whoare or can become pregnant. In this manner, unnecessary counseling, forexample, to women who are no longer of child-bearing age or men who areincapable of sexual relations with such women, may be avoided.

With further reference to methods involving teratogenic drugs, it isalso preferred that the prescriber advise the patient to not share thedrug with anyone else, and particularly that the drug should be kept outof the reach of children as well as women of child-bearing potential. Inthe case of female patients, particularly female patients ofchild-bearing potential, the prescriber should give the patient apregnancy test, preferably a serum pregnancy test, prior to and duringtreatment with the teratogenic drug. To begin receiving the teratogenicdrug and to continue taking the drug, female patients of child-bearingpotential should continue to have negative pregnancy tests. The patientis also preferably counseled by the prescriber to discard or return tothe prescriber, pharmacy, manufacturer or distributor any unused portionof the prescribed drug.

As would be apparent to one of ordinary skill in the art, once armedwith the teachings of the present application, one or more aspects ofthe counseling described above may be applicable, in certaincircumstances, for drugs other than teratogenic drugs.

In addition to receiving counseling on the drug being prescribed,including counseling, for example, on birth control, and prior toreceiving a prescription for the drug, the methods of the presentinvention preferably involve requiring the patient to fill out aninformed consent form which is signed by the prescriber, as well as thepatient. The prescriber should retain a copy of the informed consentform for his/her records. Verification that the patient has givenhis/her informed consent may also be registered in the computer readablestorage medium. Preferably, this verification is provided by theprescriber, and may be included, for example, with the patientregistration information and risk group assignment. It has surprisinglybeen found that by having the prescriber, rather than the pharmacy,verify the patient's informed consent, the methods of the presentinvention may operate more efficiently, leading to better compliance,and hence decreased risk that the adverse side effect will occur, may beachieved.

By filling out and signing an informed consent form, the patientacknowledges that he/she understands the risks associated with takingthe drug. In the informed consent form, the patient preferably agrees tocomply with the risk avoidance measures provided, and to behave in amanner which is consistent with the prescriber's counsel. For example,in cases involving, for example, teratogenic drugs, the patient mayagree to use at least one form of birth control, with female patientsagreeing to use at least two forms of birth control. In preferredembodiments, where the patient's risk group assignment so dictates, thepatient will agree to undergo periodic diagnostic testing relevant tothe risk that the adverse side effect to be avoided may occur or beoccurring. In preferred embodiments involving teratogenic drugs, femalepatients preferably agree also to undergo pregnancy testing, preferablyserum pregnancy testing, before, during and after treatment with theteratogenic drug. Female patients preferably will also acknowledge that,at the time they are being prescribed the drug, especially teratogenicdrugs, they are not pregnant, they will immediately stop taking the drugif they become pregnant, and they will not try to become pregnant for atleast 4 weeks after treatment with the drug is terminated. Femalepatients, especially female patients for whom a teratogenic drug will beadministered, preferably further agree to contact their prescriber ifthey wish to change one or more of the birth control methods being usedand to have an additional pregnancy test if a menstrual period ismissed. Female patients, especially female patients to be treated withteratogenic drugs, will preferably agree also to not breast-feed whilebeing treated with the drug.

Male patients who are being prescribed the drugs according to themethods described herein, especially teratogenic drugs, will preferablyagree to avoid having unprotected sexual relations with a woman,particularly a woman of child-bearing potential during treatment withthe drug. In doing so, male patients will preferably further agree touse a condom during sexual relations with a woman, with latex condomsbeing preferred. Both male and female patients will also preferablyagree to not share the drug with anyone, and to acknowledge that theycannot donate blood while taking the drug, with male patients agreeingalso to not donate sperm while taking the drug. In addition, thepatients will preferably agree to take part in a confidential patientsurvey, for example, before, during and after treatment with the drug.The patient survey provides information, for example, to the prescriber,manufacturer and/or distributor of the drug, as well as any group orbody which may be established to generally provide oversight on thedistribution of the drug, on information regarding the general lifestyleof the patient, including detailed information on the patient's sexualbehavior. In this manner, the survey may assist in identifying patientswho engage in risky behavior, as well as patients who are non-compliantwith the methods described herein. Such risky behavior and/ornon-compliance may lead to a suspension or intervention of the patient'streatment with the drug, with re-education being provided to thepatient.

The information obtained from the survey is preferably also entered intothe computer readable storage medium. Once entered into the computerreadable storage medium, the prescriber, manufacturer and/or distributorof the drug may be able to glean therefrom information regarding thelevel of risk associated with the administration of the involved drug tothe various patients. Accordingly, it may be possible to identify, fromamong the entire population of registered patients, one or moresubpopulations of patients for which the involved drug may be morelikely to be contraindicated. For example, it may be possible toidentify a subpopulation of female patients who are capable of becomingpregnant and/or a subpopulation of male patients who are capable ofimpregnating female patients. Preferably, the counseling informationdiscussed above relating to exposure of a foetus to a teratogenic drugmay then be addressed primarily to this subpopulation of patients.

If the risk is considered to be acceptable, the patient may continue toreceive the drug, using the methods described herein. If the risk isconsidered to be unacceptable, additional counseling may be provided tothe patient or, if necessary, treatment of the patient with the involveddrug may be terminated, with alternate treatment modalities beingprovided. In preferred embodiments, female patients will agree tocomplete a patient survey at least once every month, with male patientsagreeing to complete a patient survey at least once every three to sixmonths. The survey may be conducted by mail, facsimile transmission,on-line transmission or by telephone. Preferably, the survey isconducted by telephone through the use of an integrated voice responsesystem (IVR).

After the patient has received counseling as described above, and hasalso filled out and signed an informed consent form, and it isdetermined that the drug which is to be prescribed is notcontraindicated for the patient (such as, for example, a negativepregnancy test in the case of female patients for whom a prescription isdesired for a teratogenic drug), the prescriber may prescribe the drugto the patient. In preferred embodiments of the present invention, theamount of the drug which is prescribed to the patient is for a limitedamount, preferably no more than about 28 days. Refills for the drug willnot be permitted without a renewal prescription from the prescriber, asdiscussed in detail below. In order to have the prescription filled, thepatient preferably presents the prescription and the informed consentform to a pharmacy who has been registered, as discussed above. It iscontemplated that the patient may bring the prescription to anunregistered pharmacy. If so, the pharmacy may take steps to becomeregistered, for example, by immediately contacting the manufacturer ofthe drug. Once registration of the pharmacy is completed, thedistribution procedure described herein may resume, per the discussionhereinafter. Of course, this may introduce a delay into the prescriptionprocess, and the patient may desire to take the prescription for thedrug to an alternate, registered pharmacy. If the patient does notpresent a completed informed consent form to the pharmacy, or ifverification of such informed consent has not previously been registeredin the computer readable storage medium, the prescription may not befilled. In this case, pharmacy may contact the prescribing prescriber tohave an informed consent form filled out for the patient.

The drug is preferably supplied to the pharmacy (as well as the patient)in packaging, such as individual blister packs, which includes warningsregarding the risks associated with the drug, as well as the importanceof various aspects of the present methods such as, for example,pregnancy testing and the use of contraception (in the case ofteratogenic drugs), and the dangers associated with sharing the drugwith others, among other aspects.

As noted above, the drug is preferably prescribed and dispensed to thepatient in a limited amount, with a prescription amount of no more thanabout 28 days being preferred, and preferably with no refills beingpermitted. Thus, for the patient to obtain an additional prescription,it is generally necessary for the patient to have a follow-up visit withthe prescriber. Such a follow-up visit preferably takes place at leasteach time the patient requires a renewal of the prescription, andpossibly more often if the patient requires, for example, additionalcounseling. At the follow-up visit, the patient will preferably receiveadditional counseling regarding the risks and benefits associated withtaking the drug, as well as further counseling on birth control (ifapplicable). The patient will also preferably complete an additionalpatient survey to provide current information regarding their lifestyle,including their sexual behavior and, if female of childbearingpotential, be administered a new pregnancy test. After receiving thecounseling and completing the patient survey, and if the pregnancy testsfor female patients are negative, the prescriber may fill out a newprescription for the drug. As with the original prescription, therenewal prescription is preferably for a limited period of time, with nomore than about 28 days being more preferred.

In certain embodiments, the prescriber may also receive reminders, forexample, via mail, facsimile, or on-line transmission, from themanufacturer, distributor or other group or body providing oversight ondrug distribution, that the prescriber has prescribed a hazardous drugto patients which may be contraindicated, and that the involved patientsmay require additional counseling and diagnostic testing. Such remindersmay preferably be delivered to the prescriber, for example, from about14 to about 21 days after the previous prescription was filled.

As with the original prescription from the prescriber, the patientshould present all renewal prescriptions to a registered pharmacy. Priorto filling out the prescription and dispensing the drug, the pharmacypreferably confirms, for example, via a standard on-line transmission orvia telephone via IVR that the patient has been registered and iseligible to receive the drug. When patient eligibility has beenconfirmed, the pharmacy may dispense the drug to the patient. If thepatient is ineligible, the pharmacy generally may not dispense the drugto the patient. The pharmacy may then contact, for example, theprescribing prescriber or the manufacturer of the drug to initiatepatient registration. In preferred form, the pharmacy will be precludedfrom dispensing the drug if the patient has more than about 7 days ofdrug supply from the previous prescription, and/or if the newprescription was written more than about 14 days before the date thepatient visits the pharmacy to have it filled.

The registration into one or more computer readable storage media of theprescriber, pharmacy and patient, according to the methods describedherein, provide a means to monitor and authorize distribution ofcontraindicated drugs, including teratogenic drugs. Thus, the computerreadable storage media may serve to deny access to, dispensing of, orprescriptions for contraindicated drugs, including teratogenic drugs, topatients, pharmacies or prescribers who fail to abide by the methods ofthe present invention. As noted above, prescribers who are notregistered in a computer readable storage medium generally may notprescribe the drug, and pharmacys who are not registered generally maynot dispense the drug. Similarly, the drugs generally may not beprescribed, and/or dispensed to patients who are not registered in acomputer readable storage medium. In addition, patients may be requiredto present an informed consent form to the pharmacy. Unless such a formis presented to the pharmacy, or verification of such informed consenthas been provided by the prescriber and registered in the computerreadable media, the patient generally may not receive the prescriptionfor the drug. As noted above, only limited amounts of the drug may beprescribed to the patient, with no refill prescriptions being permitted.

In certain embodiments of the invention, the methods may require thatthe registered pharmacy consult the computer readable medium to retrievea prescription approval code before dispensing the drug to the patient.This approval code is preferably not provided unless the prescriber, thepharmacy, the patient, the patient's risk group and the patient'sinformed consent have been properly registered in the storage medium.Additionally, depending upon the risk group assignment, generation ofthe prescription approval code may further require the registration inthe storage medium of the additional set of information, includingperiodic surveys and the results of diagnostic tests, as have beendefined as being relevant to the risk group assignment. Thus, to complywith the present methods and receive approval to dispense the drug asprescribed, the registered pharmacy need only retrieve the approvalcode. If the prescription approval code is not forthcoming, the patientmay be directed to complete the necessary survey, for example, bytelephone, or may be directed back to the prescriber for completion ofnecessary diagnostic tests. In this manner, the effort required by thepharmacy is minimized, and greater compliance with the present methodsmay efficiently and advantageously be achieved. Additionally, theembodiments described herein may provide greater assurance that allrequired further information, as is appropriate to the patient's riskgroup assignment, has been obtained before the drug is dispensed to thepatient, and thereby minimize the risk that an adverse side effect willoccur.

While the delivery of teratogenic drugs is an aspect of the presentinvention which has clearly apparent benefit, other types of drugs mayalso beneficially be prescribed and delivered in accordance with one ormore embodiments hereof and all are contemplated hereby. For example,the methods of the present invention may be used for delivery of a drugwhich is known or suspected of causing liver damage in many patients whotake the drug. One such drug is isoniazid, a widely known treatment fortuburculosis (TB). In following a method of the present invention, aregistered physician may wish to prescribe isoniazid to a patient whohas tested positive for TB. The physician may register the patient in acomputer readable storage medium, along with certain informationregarding the patient's age, medical condition, and so on. If thepatient is a young adult, for example, and presents with no othercomplicating risk factors, the patient may be assigned to a risk groupthat is designated to receive counseling regarding certain behavior,such as the concomitant use of alcohol, that is to be avoided. Thepatient may be fully informed of the risks of liver damage that mayresult from taking isoniazid, and is preferably counseled to avoiddrinking any alcoholic beverages while undergoing treatment with thedrug. Preferably, the patient signs an informed consent form, and theprescribing physician transmits verification of the informed consent,along with the patient's registration form and risk group assignment tothe computer readable storage medium. The physician then provides thepatient with a prescription for the isoniazid. Upon presentation of theprescription to a registered pharmacy, the computer readable storagemedium is consulted to verify that the patient and prescriber areregistered therein, and that the patient's risk group assignment andinformed consent have been provided.

If the patient's risk group assignment so indicates, certain diagnostictests may additionally be required, so that baseline data may beobtained, before the prescription will be approved for filling. Thepatient's risk group may indicate, for example, that serum liver enzymesshould be evaluated on a monthly basis. Under these circumstances, theprescription will preferably be filled for no more than about 30 days.

The patient will also preferably be advised that completion of a monthlysurvey will be required. This survey may include a questionnaire whichis probative of the patient's alcohol consumption over the past month.The survey may also include questions which are probative of certainsymptoms which may be indicative of the early onset of liver damage orother side effects known or suspected of being caused by isoniazid.Additionally, questions regarding the patient's concomitant use of otherdrugs which are known to be hazardous when taken in combination withisoniazid may be asked. Preferably, this survey is conductedtelephonically, using an integrated voice response system, and theresponses are entered in the storage medium. Based upon the patient'sresponses, the patient's risk group assignment is adjusted or left thesame, as may be appropriate.

The patient is preferably further instructed that periodic diagnostictesting may also be necessary for continued approval of a prescription.Preferably, the diagnostic testing will include an assay of thepatient's serum liver enzyme levels, to screen for early signs of liverdamage. Additionally, the diagnostic testing may include screens for thepresence of other drugs known to also cause liver damage, or to behazardous if taken in combination with isoniazid. A prescriptionapproval code generally will not be generated for subsequentprescriptions or refills until such periodic tests have been performedand satisfactory results entered into the computer readable storagemedium. If a prescription approval code is not received by the pharmacy,the patient is directed to complete the requisite survey or tests, or toreturn to the doctor for further consultation.

If the test results or survey indicate that the risk of liver damage hasincreased, the patient's risk group assignment may be changed, or thepatient will be directed to consult with the prescriber before anyfurther isoniazid may be dispensed. In this way, the development of theadverse side effect of concern may be monitored. For example, if thetests indicate that some liver enzymes are marginally elevated, thepatient's risk group status may be changed from a first risk group to asecond risk group. As a member of this second risk group, the patientmay be required to undergo additional diagnostic testing before approvalwill be given to receive the drug. Such testing may include, forexample, liver function tests, to further diagnose the level of cellulardamage potentially being caused by the isoniazid, or the combination ofisoniazid and other drugs, such as alcohol. In more extreme cases, adiagnostic ultrasound of the liver, or even a liver biopsy may even beindicated. Ultimately, if the risk of continued administration becomesso great that it outweighs the possible benefits of continued treatmentwith isoniazid, the patient may be assigned to a risk group whichindicates that the drug may no longer be dispensed to that patient.

The methods of the present invention may similarly be employed, forexample, where the patient is undergoing treatment for infection withthe Human Immunodeficiency Virus (HIV). Patients who test positive forHIV may be treated with one or more drugs to combat the onset of theAcquired Immune Deficiency Syndrome (AIDS). Frequently, HIV positivepatients are administered an “AIDS cocktail” of several drugs including,for example, a combination of one or more inhibitors of viral proteaseand reverse transcriptase. By following the methods of the presentinvention, the patient may continue to receive the combination of drugs,while the risk of adverse side effects from administration of the drugsmay be minimized. Additionally, the methods of the present invention maybe desirably and advantageously used to educate and reinforce theactions and behaviors of patients who are taking a drug, as well asprescribers who prescribe the drug and pharmacies which dispense thedrug.

As with methods of the invention previously described, when a patienthas tested positive for HIV, a registered prescriber may obtainbackground information on the patient and see that a registration formis completed so that the patient may be registered in the computerreadable storage medium. The prescriber may prescribe one or more drugsto the patient, including drugs which may be known or suspected ofcausing adverse side effects, either alone or in combination with eachother or with other drugs. Depending upon the drugs prescribed, and alsoupon information which the prescriber will preferably obtain regardingthe patient's medical history, physical condition and lifestyle, thepatient will preferably be assigned to at least one risk group. Basedupon this risk group assignment, the patient will preferably receiveeducational materials and counseling regarding the risks associated withthe prescribed drugs, and be advised of the importance of the treatmentregimen. The patient will also preferably receive counseling regardingthe risk of spreading the disease to others, including a foetus whichmay be carried by the patient and any recipient of a bodily fluid of thepatient. Thus, the patient may be counseled regarding the preferentialuse of one or more methods of birth control, and may also be providedwith a contraceptive device by the prescriber. Additionally, the patientwill preferably be counseled not to share any of the drugs with others,and to avoid taking any medications not prescribed. In this way, thepatient will preferably be counseled both as to methods for minimizingthe spread of the disease, as well as to methods for avoiding theoccurrence of one or more side effects which may result from the takingof the medication. Preferably, upon full disclosure of all risksinherent in the treatment regimen, the prescriber will obtain andregister in the computer readable storage medium the informed consent ofthe patient to receive the medication and to comply with the methodsdescribed herein for avoiding the occurrence of one or more side effectswhich may result from taking the drug or drugs prescribed.

To facilitate compliance with the methods of the present invention, andto minimize the likelihood of the occurrence of a known or suspectedadverse side effect from treatment with the prescribed drug or drugs, itis preferable that when prescriptions for the drug are presented to aregistered pharmacy, the computer readable storage medium is consultedto retrieve a prescription approval code before the drug is dispensed tothe patient. In order for a prescription approval code to be generated,and based upon the patient's risk group assignment, the patient may berequired to provide additional information, which may then be entered inthe storage medium before approval of the prescription may be provided.For example, the patient may be required to undergo certain diagnostictests. In a patient with HIV, for example, testing for viral load may berequired, both initially and on a periodic basis, so that dosing of themedication may be adjusted, as necessary. The patient may also berequired to complete a survey which asks questions probative of thelikelihood that the patient is taking other medications, or beginning toexhibit symptoms which may be of importance to the selection andimplementation of a therapeutic regimen. Such additional information maybe required both before the initiation of treatment and on a periodicbasis during treatment, as new prescriptions and prescription refillsare generated. Based upon the information provided by the patient, andthe results of any diagnostic tests which have been performed, thepatient's risk group assignment may stay the same, or may be changed, asindicated. The patient's risk group assignment may also be changed basedupon the length of time the patient has been receiving a given drug ormedication.

A periodic patient survey may serve both to remind the patient of therequirements of the drug distribution program, and to obtain informationwhich may be probative of the risk that an adverse side effect mayoccur. For example, the survey may include questions probative of thepatient's behavior as it relates to the sharing of medication with otherHIV positive individuals, and the patient's compliance with measures foravoiding the spread of the disease. Additionally, the survey may includequestions regarding other drugs, medications or treatments which thepatient might be availing themselves of, which would impact the risk ofan adverse side effect occurring.

The survey may also contain questions which are probative of the onsetof certain symptoms which may be indicative of the need for changes inthe patient's treatment regimen. For example, some questions may beprobative of the onset of depression in the patient, a common occurrenceamongst AIDS sufferers. Answers to questions in the survey that areindicative of depression, for example, may cause the patient's riskgroup assignment to change such that the patient is directed to returnto the prescriber for determination of whether treatment with ananti-depressant drug is indicated. Similarly, certain drugs, such asprotease inhibitors, for example, may lead to abnormal redistribution offat in certain patients. This symptom may be seen in conjunction withcertain metabolic defects and may in turn be symptomatic of conditionssuch as high blood sugar and high cholesterol. Questions relating tothis abnormality may be included on the survey, and answers whichindicate that the patient has noticed such physical changes may lead tothe assignment of the patient to a risk group in which diagnostic testsprobative of the metabolic abnormalities are required before furtheraccess to the drug in question is permitted.

As with the survey, the diagnostic testing which the patient may berequired to undergo may vary with, and preferably is appropriate to, thepatient's risk group assignment. In addition to testing for thepatient's viral load, periodic diagnostic testing may be appropriate,for example, to evaluate the level of one or more medications in thepatient. Dosage of reverse transcriptase inhibitors, for example, may becritical to the risk of occurrence of an adverse side effect. At thesame time, various drugs which are often used in combination may sharesimilar metabolic pathways, so that the addition of a second drug to thetreatment regimen may greatly affect the pharmacokinetics of the firstdrug, thereby necessitating an adjustment in the dose of the first drug.In the case of treatment with an “AIDS cocktail” containing, forexample, the use of ritonavir, a well-known protease inhibitor, maygreatly impact the bioavailability of other protease inhibitors,requiring that the dose of the other protease inhibitors be reduced.Accordingly, the inclusion of ritonavir in the patient's treatmentregimen may initiate a change in risk-group assignment, which in turnrequires that diagnostic testing to evaluate the blood levels of otherconcomitantly administered protease inhibitors be done on a periodicbasis.

Similarly, the addition of other drugs to the treatment regimen, eitherby the prescribing physician, or by another physician whom the patientmight visit, may interfere with the initial treatment regimen prescribedby the registered prescriber. For example, AIDS patients often developmycobacterial infections such as tuberculosis. An infectious diseasespecialist may prescribe one of a class of drugs known as rifamycins,such as rifampin or rifabutin, to treat such infections. Rifamycins areknown to accelerate the metabolism of many protease inhibitors, however,so that upon initiation of treatment with a rifamycin, the effectivenessof the protease inhibitors may be greatly reduced, unless the dosage ofthose drugs is adjusted appropriately. Thus, when the patient is beingtreated with a protease inhibitor, the survey may include, for example,questions regarding the possible concurrent use of a rifamycin. If thesurvey results indicate that the two types of drugs are being usedconcurrently, the patient's risk group assignment is changed, such thatthe patient may be referred back to the prescriber for an adjustment indosage, or the patient may be directed to undergo diagnostic testing toassure that a sufficient level of the protease inhibitor is still beingmaintained. Similarly, where the registered prescriber adds aprescription for a rifamycin to the treatment regimen of a registeredpatient who is also receiving a protease inhibitor, entry of theprescription into the computer readable storage medium may trigger anautomatic change in risk group assignment, such that approval of theprescription will not be generated without further modification of thedosage of the protease inhibitor. In this way, the methods of thepresent invention may be advantageously utilized to maintain the properdosing of one or more drugs, to minimize the likelihood of theoccurrence of an adverse side effect from the concomitant use of suchdrugs, or the addition of other drugs to a treatment regimen, toencourage proper disclosure of the risks associated with the taking ofone or more drugs, to minimize the risk that a contraindicatedindividual will be exposed to the potentially hazardous drugs, and toassist in generating patient compliance with treatment protocols andavoidance of behavior known to increase the risk that the disease willbe spread to others.

Various modifications of the invention, in addition to those describedherein, will be apparent to those skilled in the art from the foregoingdescription. Such modifications are also intended to fall within thescope of the appended claims.

1. A method of treating a male patient, suffering from erythema nodosumleprosum, with thalidomide, by permitting prescriptions for thalidomideto be filled by a pharmacy only after the pharmacy has retrieved aprescription approval code for the prescription, comprising thefollowing steps: (a) via a non-transitory computer readable storagemedium, registering a prescriber and the pharmacy with a distributor ofthalidomide; (b) determining whether the patient is able to understandand carry out instructions; (c) upon determination that the patient isable to carry out the instructions, providing verbal and writtenwarnings of the hazard of taking thalidomide and exposing fetus to thedrug; (d) further providing verbal and written warnings of the risk ofpossible contraception failure and of the need to use barriercontraception when having sexual intercourse with women of child bearingpotential; (e) obtaining acknowledgement of said warnings from thepatient; (f) providing the prescription for thalidomide to the patientfrom the prescriber; (g) via a non-transitory computer readable storagemedium, registering the patient with the distributor; (h) upon obtainingthe acknowledgement and registrations, generating the prescriptionapproval code, and via a non-transitory computer readable storagemedium, retrieving the prescription approval code by the pharmacy beforethe prescription is filled; and (i) upon retrieving the prescriptionapproval code, administering thalidomide to the patient.
 2. The methodof claim 1, wherein the acknowledgement requires the patient'sacknowledgement of one or more of the following: (a) the understandingthat thalidomide must not be taken if unprotected sex cannot be avoided;(b) the understanding of potential birth defects; (c) that the patienthas been advised of the need for barrier contraception by theprescriber; (d) the obligation to inform the prescriber if the patient'ssexual partner is suspected of becoming or being pregnant; (e) thatthalidomide is solely for the use of the patient himself and must not beshared with any other person; (f) that the patient has read theinformation brochure or viewed the information film on thalidomide; (g)that the semen or blood must not be donated during the thalidomidetreatment; (h) that all of the patient's inquiries regarding thalidomidetreatment have been answered by the prescribing physician; or (i) thepatient's understanding that participation in a survey and patientregistry is required during the thalidomide treatment.
 3. The method ofclaim 1 further comprising providing the patient, prior to generation ofthe approval code, with warnings of the side effects associated withadministration of thalidomide, wherein said side effects arenon-teratogenic side effects.
 4. The method of claim 1 furthercomprising obtaining a written authorization by the prescriber prior togeneration of the approval code.
 5. The method of claim 1, wherein theacknowledgement is a written informed consent.